Transfusional Hemosiderosis, Transfusional Iron Overload
Conditions
Keywords
iron overload, cardiac iron, haemosiderosis, myocardial T2*, left ventricular ejection fraction, LVEF, cardiac dysfunction, thalassaemia, Diamond Blackfan anemia, DBA, sideroblastic anemia, myelodysplastic syndromes, MDS (low and INT-1 risk as per the IPSS for MDS), liver MRI, deferasirox, deferoxamine, ICL670, DFO, cardiovascular magnetic resonance imaging
Brief summary
This is a clinical research study in patients who have iron overload in the heart due to chronic blood transfusions. The study will have 2 treatment groups and will compare the safety and efficacy of chelation therapy with a medicine called deferasirox (ICL670) with another medicine called deferoxamine (DFO). The study is aimed at finding out which of the two medicines is the best for treating iron overload in the heart. Patients will be treated for 12 months (core study phase). Patients who complete the core study phase will be offered to continue their study treatment in a 12 months extension phase. During the core and extension, the effects of treatment on iron overload in the heart and the liver will be evaluated using specific magnetic resonance imaging (MRI) assessments.
Interventions
DRUGCore Study: Deferasirox
20 mg/kg/day once daily (od) for 2 weeks, followed by 30 mg/kg/day od for 1 week and a subsequent continuation of 40 mg/kg/day
DRUGCore Study: Deferoxamine
50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week
DRUGExtension: deferoxamine to deferasirox
40 mg/kg deferasirox once daily administered 30 minutes before taking food.
DRUGExtension: deferasirox to deferoxamine
DFO at a target range of 50 mg/kg/day to 60 mg/kg/day via subcutaneous (sc) infusion lasting a period of 8 to 12 hrs administered for 5 to 7 days per week,
DRUGDeferasirox
DRUGDeferoxamine
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients, aged 10 years and above, with β-thalassemia major or DBA or sideroblastic anemia on chronic transfusion therapy, having given written consent to participate in the study. * Patients with cardiac iron as measured by a myocardial T2\* value that is ≥ 6ms but not ≥ 20 ms. * Patients with a lifetime history of at least 50 units of red cell transfusions, and must be receiving at least ≥10 units/yr of red blood cells transfusions. * Patients with a left ventricular ejection fraction (LVEF) ≥ 56 % as determined by cardiovascular magnetic resonance (CMR). * Patients with liver iron content (LIC) value ≥ 3 mg Fe / g dw, as determined by liver MRI.
Exclusion criteria
* Patients with clinical symptoms of cardiac dysfunction. * Patients unable to undergo study assessments including MRI * Patients participating in another clinical trial or receiving an investigational drug. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment | 12 Month | Non- inferiority in efficacy of deferasirox compared to deferoxamine (DFO) in treating cardiac iron overload as measured by T2\*. A non-inferiority margin of 0.9 (90%) was applied. Due to limitations in performing heart biopsies, T2\* (T2 star), a Magnetic Resonance (MR) relaxation parameter expressed in milliseconds, as is an important tool to noninvasively quantify cardiac iron concentration. Studies have shown that myocardial T2\* evaluations may predict cardiac events, e.g., impaired (\<56%) left ventricular ejection fraction (LVEF) is prevalent among patients with low T2\*: found in 62% of patients with T2\*\<8 ms; 20% with T2\* of 8-12 ms; and in 5% with T2\* \>12 ms (Tanner 2006) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Core Study: Cardiac Function After 6 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF) | 6 Month | An absolute change from baseline in LVEF after 6 months treatment with deferasirox and DFO was summarized |
| Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment | 6 Month | Summary statistics of T2\* ratio Month 6/baseline |
| Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | 6 Month, 12 Month | An absolute change from baseline in LVESVI after 6 and 12 months treatment with deferasirox and DFO was summarized. Changes in cardiovascular magnetic resonance (CMR) measured left ventricular end systolic after 6 and 12 months treatment. Left ventricular (LV) end-systolic volume indexed to body surface area (ESVI) is a simple yet powerful echocardiographic marker of LV remodeling that can be measured easily. Left ventricular (LV) end-systolic volume (ESV) has been shown to be an important determinant of survival after myocardial infarction (MI) |
| Core Study: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | 6 Month, 12 Month | An absolute change from baseline in LVEDVI after 6, and 12 months treatment with deferasirox and DFO was summarized |
| Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI) | 6 Month, 12 Month | An absolute change from baseline in LVMI after 6, and 12 months treatment with deferasirox and DFO was summarized |
| Core Study: Cardiac Function and the Proportion of Patients Dropping Out Due to Cardiac Dysfunction After Treatment With Deferasirox vs. Deferoxamine | 12 Month | The number of patients withdrawn from the study due to LVEF \<50%, T2\* \<6 ms or significant decreases in T2\* ≥ 33% from baseline was provided per treatment group. |
| Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period. | 12 Month | Number of patients with adverse events, serious adverse events and death |
| Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Area Under the Plasma Concentration-time Curve for a Dosing Interval (AUCtau) | 12 Month | The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, area under the plasma concentration-time curve for a dosing interval (AUCtau) |
| Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Cmax) | 12 Month | The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, maximum plasma concentration (Cmax) |
| Core Study: Cardiac Function After 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF) | 12 Month | An absolute change from baseline in LVEF after 12 months treatment with deferasirox and compared to.DFO was tested using an analysis of covariance model including baseline left ventricular ejection fraction (LVEF) as a covariate. |
| Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Months 6, 12, 18 and 24 | The measured T2\* values, the ratio (post-baseline / baseline T2\*) at Month 6, 12, 18 and 24 was summarized for FAS population along with two-sided 95% CIs. The geometric means of the ratio was presented for all treatment groups |
| Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Months 6, 12, 18 and 24 | Cardiac function endpoints (LVEF) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline |
| Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Months 6, 12, 18 and 24 | Cardiac function endpoints (LVESVI) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline |
| Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Months 6, 12, 18 and 24 | Cardiac function endpoint (LVEDVI ) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline |
| Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Months 6, 12, 18 and 24 | Cardiac function endpoints (LVMI) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes |
| Extension Study: The Cardiac Iron Concentration From T2* Values | Months 6, 12, 18 and 24 | Cardiac iron concentration (derived from T2\* values) at baseline, Months 6, 12, 18 and 24 were summarized by descriptive statistics. The absolute change from baseline at Months 6, 12, 18 and 24 were also summarized by treatment group. Lliver iron concentration is expressed in units (mg of iron / g of liver tissue dry weight (dw) |
| Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Months 6, 12, 18 and 24 | Results of liver iron content (LIC) measurements by MRI was summarized by descriptive statistics. The absolute value and the absolute change from baseline in LIC at Months 6, 12, 18 and 24 were provided by treatment group. |
| Extension Study: Change in Serum Ferritin From Baseline by Month | Months 6, 12, 18 and 24 | Serum ferritin values was summarized by descriptive statistics. Absolute value and the absolute change from baseline in serum ferritin by month was provided by treatment group. |
| Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Tmax) | 12 Month | The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, time to reach maximum plasma concentration (Tmax) |
| Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data | Month 1 and month 2 (pre-dose, 1,2 and 4 hours post-dose) | The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. For trough concentration assessments, a 2-mL blood sample was to be taken on arrival at the study site, i.e. prior to the patient receiving the daily deferasirox dose (pre-dose blood sample). A second 2-mL blood sample was to be taken 2 hours later (post-dose sample). At all other visits (Visits 3 - 14), a pre-dose sample was to be taken. For PK profile assessments, 3 blood samples were taken after 1, 2, and 4 hours post-dose in addition to the 2-mL pre-dose |
Countries
Canada, China, Cyprus, Egypt, Italy, Lebanon, Taiwan, Thailand, Turkey (Türkiye), United Arab Emirates, United Kingdom
Participant flow
Pre-assignment details
Patients randomized to 1 of 2 treatment grps ICL or DFO, 20 mg/kg/day once daily for 2 wks, followed by 30 mg/kg/day od for 1 wk and 40 mg/kg/day od (DFO) target dose of 50 to 60 mg/kg/day 8 to 12 hour for 5 to 7 days/wk. In ext. pts could either stay in the same grp from core or could switch grps: ICL to ICL, DFO to DFO, DFO to ICL and ICL to DFO
Participants by arm
| Arm | Count |
|---|---|
| Core: Deferasirox (ICL) 20 mg/kg/day once daily (od) for 2 weeks, followed by 30 mg/kg/day od for 1 week and a subsequent continuation of 40 mg/kg/day | 98 |
| Core: Deferoxamine (DFO) 50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week | 99 |
| Total | 197 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Core Study | Abnormal test procedure result(s) | 3 | 2 | 0 | 0 |
| Core Study | Death | 1 | 1 | 0 | 0 |
| Core Study | Lost to Follow-up | 3 | 2 | 0 | 0 |
| Core Study | Patient withdrew consent | 7 | 12 | 0 | 0 |
| Core Study | Protocol Violation | 1 | 2 | 0 | 0 |
| Core Study | Unsatisfactory therapeutic effect | 1 | 2 | 0 | 0 |
| Extension Study | Abnormal test procedure results | 0 | 1 | 1 | 1 |
| Extension Study | Adverse Event | 1 | 0 | 2 | 0 |
| Extension Study | Death | 1 | 0 | 0 | 0 |
| Extension Study | Lost to Follow-up | 1 | 1 | 2 | 0 |
| Extension Study | Unsatisfactory therapeutic effect | 4 | 1 | 1 | 0 |
| Extension Study | Withdrawal by Subject | 2 | 2 | 3 | 0 |
Baseline characteristics
| Characteristic | Core: Deferasirox (ICL) | Core: Deferoxamine (DFO) | Total |
|---|---|---|---|
| Age, Continuous | 19.9 Years STANDARD_DEVIATION 6.53 | 19.7 Years STANDARD_DEVIATION 6.32 | 19.8 Years STANDARD_DEVIATION 6.41 |
| Sex: Female, Male Female | 40 Participants | 42 Participants | 82 Participants |
| Sex: Female, Male Male | 58 Participants | 57 Participants | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 60 / 96 | 58 / 91 | 56 / 73 | 19 / 29 | 36 / 42 | 1 / 1 |
| serious Total, serious adverse events | 10 / 96 | 10 / 91 | 14 / 73 | 4 / 29 | 9 / 42 | 0 / 1 |
Outcome results
Primary
Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment
Non- inferiority in efficacy of deferasirox compared to deferoxamine (DFO) in treating cardiac iron overload as measured by T2\*. A non-inferiority margin of 0.9 (90%) was applied. Due to limitations in performing heart biopsies, T2\* (T2 star), a Magnetic Resonance (MR) relaxation parameter expressed in milliseconds, as is an important tool to noninvasively quantify cardiac iron concentration. Studies have shown that myocardial T2\* evaluations may predict cardiac events, e.g., impaired (\<56%) left ventricular ejection fraction (LVEF) is prevalent among patients with low T2\*: found in 62% of patients with T2\*\<8 ms; 20% with T2\* of 8-12 ms; and in 5% with T2\* \>12 ms (Tanner 2006)
Time frame: 12 Month
Population: Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2\* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment | 1.12 Millisecond | 95% Confidence Interval 3.687 |
| Core: Deferoxamine (DFO) | Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment | 1.07 Millisecond | 95% Confidence Interval 2.931 |
Secondary
Core Study: Cardiac Function After 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)
An absolute change from baseline in LVEF after 12 months treatment with deferasirox and compared to.DFO was tested using an analysis of covariance model including baseline left ventricular ejection fraction (LVEF) as a covariate.
Time frame: 12 Month
Population: Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2\* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Cardiac Function After 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF) | -0.5 Percent | Standard Error 0.47 |
| Core: Deferoxamine (DFO) | Core Study: Cardiac Function After 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF) | -0.0 Percent | Standard Error 0.49 |
Secondary
Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI)
An absolute change from baseline in LVMI after 6, and 12 months treatment with deferasirox and DFO was summarized
Time frame: 6 Month, 12 Month
Population: Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2\* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI) | Change from Baseline at 6 Month (n= 85, 73) | 1.01 gram/m^2 | Standard Deviation 13.102 |
| Core: Deferasirox (ICL) | Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI) | Change from Baseline at 12 Month/EOS (n= 91, 81) | 4.13 gram/m^2 | Standard Deviation 15.055 |
| Core: Deferoxamine (DFO) | Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI) | Change from Baseline at 6 Month (n= 85, 73) | 3.32 gram/m^2 | Standard Deviation 13.585 |
| Core: Deferoxamine (DFO) | Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI) | Change from Baseline at 12 Month/EOS (n= 91, 81) | 5.25 gram/m^2 | Standard Deviation 14.973 |
Secondary
Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI)
An absolute change from baseline in LVESVI after 6 and 12 months treatment with deferasirox and DFO was summarized. Changes in cardiovascular magnetic resonance (CMR) measured left ventricular end systolic after 6 and 12 months treatment. Left ventricular (LV) end-systolic volume indexed to body surface area (ESVI) is a simple yet powerful echocardiographic marker of LV remodeling that can be measured easily. Left ventricular (LV) end-systolic volume (ESV) has been shown to be an important determinant of survival after myocardial infarction (MI)
Time frame: 6 Month, 12 Month
Population: Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2\* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Change from baseline at 6 Month (n= 85, 73) | 1.8 Milliliter | Standard Deviation 8.021 |
| Core: Deferasirox (ICL) | Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Change from Baseline at 12 Month/EOS (n= 91, 81) | 1.57 Milliliter | Standard Deviation 8.04 |
| Core: Deferoxamine (DFO) | Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Change from baseline at 6 Month (n= 85, 73) | 0.88 Milliliter | Standard Deviation 8.919 |
| Core: Deferoxamine (DFO) | Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Change from Baseline at 12 Month/EOS (n= 91, 81) | 0.10 Milliliter | Standard Deviation 10.387 |
Secondary
Core Study: Cardiac Function After 6 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)
An absolute change from baseline in LVEF after 6 months treatment with deferasirox and DFO was summarized
Time frame: 6 Month
Population: Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2\* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Cardiac Function After 6 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF) | -0.95 Percent | Standard Deviation 4.485 |
| Core: Deferoxamine (DFO) | Core Study: Cardiac Function After 6 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF) | -0.37 Percent | Standard Deviation 4.389 |
Secondary
Core Study: Cardiac Function and the Proportion of Patients Dropping Out Due to Cardiac Dysfunction After Treatment With Deferasirox vs. Deferoxamine
The number of patients withdrawn from the study due to LVEF \<50%, T2\* \<6 ms or significant decreases in T2\* ≥ 33% from baseline was provided per treatment group.
Time frame: 12 Month
Population: Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2\* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Cardiac Function and the Proportion of Patients Dropping Out Due to Cardiac Dysfunction After Treatment With Deferasirox vs. Deferoxamine | 3 Participants |
| Core: Deferoxamine (DFO) | Core Study: Cardiac Function and the Proportion of Patients Dropping Out Due to Cardiac Dysfunction After Treatment With Deferasirox vs. Deferoxamine | 2 Participants |
Secondary
Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment
Summary statistics of T2\* ratio Month 6/baseline
Time frame: 6 Month
Population: Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2\* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment | 1.04 Ratio | 95% Confidence Interval 4.752 |
| Core: Deferoxamine (DFO) | Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment | 1.04 Ratio | 95% Confidence Interval 4.417 |
Secondary
Core Study: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)
An absolute change from baseline in LVEDVI after 6, and 12 months treatment with deferasirox and DFO was summarized
Time frame: 6 Month, 12 Month
Population: Per Protocol Set (PPS) consisted of all randomized patients who received at least 6 months of randomized study drug, had a T2\* value assessed at least 150 days after randomization, adhered to the major inclusion and none of the major exclusion criteria, and had no major protocol deviations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Change from Baseline at 12 Month/EOS (n= 91, 81) | 1.79 Percent | Standard Deviation 13.122 |
| Core: Deferasirox (ICL) | Core Study: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Change from Baseline at 6 Month (n= 85, 73) | 1.81 Percent | Standard Deviation 14.515 |
| Core: Deferoxamine (DFO) | Core Study: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Change from Baseline at 6 Month (n= 85, 73) | 1.48 Percent | Standard Deviation 19.188 |
| Core: Deferoxamine (DFO) | Core Study: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Change from Baseline at 12 Month/EOS (n= 91, 81) | 1.10 Percent | Standard Deviation 20.485 |
Secondary
Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period.
Number of patients with adverse events, serious adverse events and death
Time frame: 12 Month
Population: Safety Set (SS) consisted of all randomized patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received. Treatment received is defined as first study drug administered
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period. | At least one AE | 65 Participants |
| Core: Deferasirox (ICL) | Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period. | Serious Adverse Events | 10 Participants |
| Core: Deferasirox (ICL) | Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period. | Death. None were considered related to study drug. | 1 Participants |
| Core: Deferoxamine (DFO) | Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period. | At least one AE | 69 Participants |
| Core: Deferoxamine (DFO) | Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period. | Serious Adverse Events | 10 Participants |
| Core: Deferoxamine (DFO) | Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period. | Death. None were considered related to study drug. | 1 Participants |
Secondary
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Area Under the Plasma Concentration-time Curve for a Dosing Interval (AUCtau)
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, area under the plasma concentration-time curve for a dosing interval (AUCtau)
Time frame: 12 Month
Population: Pharmacokinetic Analysis Set (PAS): PAS 2: All randomized patients who received the same dose of deferasirox for at least four consecutive days prior to PK sample collection and completed PK sample collection specified in the protocol at Visit 3 or Visit 4 (pre-dose, 1, 2, and 4 hours post-dose).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Area Under the Plasma Concentration-time Curve for a Dosing Interval (AUCtau) | 2129.70 (h.ng/mL) | Standard Deviation 930.202 |
Secondary
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Cmax)
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, maximum plasma concentration (Cmax)
Time frame: 12 Month
Population: Pharmacokinetic Analysis Set (PAS): PAS 2: All randomized patients who received the same dose of deferasirox for at least four consecutive days prior to PK sample collection and completed PK sample collection specified in the protocol at Visit 3 or Visit 4 (pre-dose, 1, 2, and 4 hours post-dose).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Cmax) | 150.09 umol/L | Standard Deviation 59.143 |
Secondary
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Tmax)
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. Descriptive statistics included the mean, median, SD, and CV, min and max. deferasirox pharmacokinetics (PK) trough levels over the 12 months of treatment and obtained PK profiles for the 40 mg/kg/day deferasirox dose, time to reach maximum plasma concentration (Tmax)
Time frame: 12 Month
Population: Pharmacokinetic Analysis Set (PAS): PAS 2: All randomized patients who received the same dose of deferasirox for at least four consecutive days prior to PK sample collection and completed PK sample collection specified in the protocol at Visit 3 or Visit 4 (pre-dose, 1, 2, and 4 hours post-dose).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Tmax) | 4.00 (h) | Inter-Quartile Range 930.202 |
Secondary
Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data
The plasma level of deferasirox (ICL670) obtained in this study was summarized descriptively. Plasma concentration was plotted by patient and by visit. For trough concentration assessments, a 2-mL blood sample was to be taken on arrival at the study site, i.e. prior to the patient receiving the daily deferasirox dose (pre-dose blood sample). A second 2-mL blood sample was to be taken 2 hours later (post-dose sample). At all other visits (Visits 3 - 14), a pre-dose sample was to be taken. For PK profile assessments, 3 blood samples were taken after 1, 2, and 4 hours post-dose in addition to the 2-mL pre-dose
Time frame: Month 1 and month 2 (pre-dose, 1,2 and 4 hours post-dose)
Population: Pharmacokinetic Analysis Set (PAS): PAS 2: All randomized patients who received the same dose of deferasirox for at least four consecutive days prior to PK sample collection and completed PK sample collection specified in the protocol at Visit 3 or Visit 4 (pre-dose, 1, 2, and 4 hours post-dose).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data | Month 1, 1 hour (post dos) | 96.32 (umol/L) | Standard Deviation 35.799 |
| Core: Deferasirox (ICL) | Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data | Month 2, 2 hour (post dose) | 177.19 (umol/L) | Standard Deviation 55.343 |
| Core: Deferasirox (ICL) | Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data | Month 1, 0 hour (predose) | 32.25 (umol/L) | Standard Deviation 21.288 |
| Core: Deferasirox (ICL) | Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data | Month 1, 2 hour (post dose) | 136.47 (umol/L) | Standard Deviation 51.831 |
| Core: Deferasirox (ICL) | Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data | Month 1, 4 hour (post dose) | 133.33 (umol/L) | Standard Deviation 62.815 |
| Core: Deferasirox (ICL) | Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data | Month 2, 0 hour (predose) | 38.66 (umol/L) | Standard Deviation 29.887 |
| Core: Deferasirox (ICL) | Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data | Month 2, 1 hour (post dose) | 119.48 (umol/L) | Standard Deviation 38.709 |
| Core: Deferasirox (ICL) | Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data | Month 2, 4 hour (post dose) | 180.76 (umol/L) | Standard Deviation 57.877 |
Secondary
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF)
Cardiac function endpoints (LVEF) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline
Time frame: Months 6, 12, 18 and 24
Population: Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase. Cardiac function parameters over time - excluding patients in Egypt sites.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 18 (n=68,26,39,1 ) | -0.1 Percent | Standard Deviation 4.84 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 24 (n= 63,25,33,1) | 0.6 Percent | Standard Deviation 4.72 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 12 (n= 66,29,42,1) | -0.5 Percent | Standard Deviation 5.02 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 6 (n=71,26,40,1) | -1.1 Percent | Standard Deviation 4.96 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 12 (n= 66,29,42,1) | 0.3 Percent | Standard Deviation 5.13 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 18 (n=68,26,39,1 ) | -0.8 Percent | Standard Deviation 5.14 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 6 (n=71,26,40,1) | -1.8 Percent | Standard Deviation 3.59 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 24 (n= 63,25,33,1) | -0.6 Percent | Standard Deviation 5.02 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 18 (n=68,26,39,1 ) | -1.3 Percent | Standard Deviation 3.74 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 6 (n=71,26,40,1) | 0.1 Percent | Standard Deviation 4.6 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 12 (n= 66,29,42,1) | 0.0 Percent | Standard Deviation 3.73 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 24 (n= 63,25,33,1) | 0.2 Percent | Standard Deviation 4.82 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 6 (n=71,26,40,1) | -1.0 Percent | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 18 (n=68,26,39,1 ) | -10.0 Percent | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 24 (n= 63,25,33,1) | -18.0 Percent | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF) | Month 12 (n= 66,29,42,1) | 0 Percent | Standard Deviation 0 |
Secondary
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)
Cardiac function endpoint (LVEDVI ) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline
Time frame: Months 6, 12, 18 and 24
Population: Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase. Cardiac function parameters over time - excluding patients in Egypt sites
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 6 (n=69,26,40,1) | 2.0 mL/m^2 | Standard Deviation 14.19 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 18 (n=67,24,35,1) | 6.5 mL/m^2 | Standard Deviation 17.8 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 12 (n=64,28,40,1) | 2.0 mL/m^2 | Standard Deviation 13.49 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 24 (n=60,23,33,0) | 3.4 mL/m^2 | Standard Deviation 21.15 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 18 (n=67,24,35,1) | 4.2 mL/m^2 | Standard Deviation 19.75 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 24 (n=60,23,33,0) | 9.5 mL/m^2 | Standard Deviation 14.6 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 12 (n=64,28,40,1) | -0.6 mL/m^2 | Standard Deviation 18.56 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 6 (n=69,26,40,1) | 3.5 mL/m^2 | Standard Deviation 21.95 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 12 (n=64,28,40,1) | 3.0 mL/m^2 | Standard Deviation 23.06 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 18 (n=67,24,35,1) | 8.3 mL/m^2 | Standard Deviation 16.08 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 6 (n=69,26,40,1) | 0.5 mL/m^2 | Standard Deviation 18.77 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 24 (n=60,23,33,0) | 5.4 mL/m^2 | Standard Deviation 13.97 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 24 (n=60,23,33,0) | NA mL/m^2 | — |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 6 (n=69,26,40,1) | 1.0 mL/m^2 | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 18 (n=67,24,35,1) | 36.0 mL/m^2 | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI) | Month 12 (n=64,28,40,1) | 4.0 mL/m^2 | Standard Deviation 0 |
Secondary
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI)
Cardiac function endpoints (LVESVI) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes from baseline
Time frame: Months 6, 12, 18 and 24
Population: Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase. Cardiac function parameters over time - excluding patients in Egypt sites.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 6 (n=69,26,40,1) | 1.7 mL/m^2 | Standard Deviation 7.98 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 12 (n=64,28,40,1 ) | 1.5 mL/m^2 | Standard Deviation 7.42 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 18 (n=67,24,35,1 ) | 2.4 mL/m^2 | Standard Deviation 10.58 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 24 (n=60,23,33,0 ) | 1.6 mL/m^2 | Standard Deviation 10.21 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 12 (n=64,28,40,1 ) | -0.8 mL/m^2 | Standard Deviation 9.74 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 18 (n=67,24,35,1 ) | 2.8 mL/m^2 | Standard Deviation 11.54 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 24 (n=60,23,33,0 ) | 4.3 mL/m^2 | Standard Deviation 8.66 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 6 (n=69,26,40,1) | 3.4 mL/m^2 | Standard Deviation 10.4 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 18 (n=67,24,35,1 ) | 4.1 mL/m^2 | Standard Deviation 6.88 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 12 (n=64,28,40,1 ) | 0.6 mL/m^2 | Standard Deviation 9.69 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 24 (n=60,23,33,0 ) | 1.7 mL/m^2 | Standard Deviation 8.56 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 6 (n=69,26,40,1) | 0 mL/m^2 | Standard Deviation 8.22 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 24 (n=60,23,33,0 ) | NA mL/m^2 | — |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 12 (n=64,28,40,1 ) | 2 mL/m^2 | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 6 (n=69,26,40,1) | 1 mL/m^2 | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI) | Month 18 (n=67,24,35,1 ) | 28.0 mL/m^2 | Standard Deviation 0 |
Secondary
Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI)
Cardiac function endpoints (LVMI) obtained by CMR at baseline, Months 6, 12, 18 and 24 were summarized by means of descriptive statistics. These analyses were conducted for the measured values as well as for the absolute changes
Time frame: Months 6, 12, 18 and 24
Population: Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase. Cardiac function parameters over time - excluding patients in Egypt sites
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 6 (n=69,26,40,1) | 1.4 gram/m^2 | Standard Deviation 12.37 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 12 (n=64,28,40,1) | 4.2 gram/m^2 | Standard Deviation 13.9 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 18 (n=67,24,35,1) | 4.8 gram/m^2 | Standard Deviation 14.37 |
| Core: Deferasirox (ICL) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 24 (n=60,23,33,0) | 5.6 gram/m^2 | Standard Deviation 13 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 12 (n=64,28,40,1) | 9.1 gram/m^2 | Standard Deviation 14.19 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 24 (n=60,23,33,0) | 6.7 gram/m^2 | Standard Deviation 14.96 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 6 (n=69,26,40,1) | 1.8 gram/m^2 | Standard Deviation 15.98 |
| Core: Deferoxamine (DFO) | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 18 (n=67,24,35,1) | -0.1 gram/m^2 | Standard Deviation 16.87 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 18 (n=67,24,35,1) | 4.0 gram/m^2 | Standard Deviation 14.39 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 24 (n=60,23,33,0) | 10.3 gram/m^2 | Standard Deviation 13.32 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 6 (n=69,26,40,1) | 3.2 gram/m^2 | Standard Deviation 13.38 |
| Extension; DFO to ICL | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 12 (n=64,28,40,1) | 3.4 gram/m^2 | Standard Deviation 16.54 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 24 (n=60,23,33,0) | NA gram/m^2 | — |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 6 (n=69,26,40,1) | -6.0 gram/m^2 | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 12 (n=64,28,40,1) | 1 gram/m^2 | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI) | Month 18 (n=67,24,35,1) | 37.0 gram/m^2 | Standard Deviation 0 |
Secondary
Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment
The measured T2\* values, the ratio (post-baseline / baseline T2\*) at Month 6, 12, 18 and 24 was summarized for FAS population along with two-sided 95% CIs. The geometric means of the ratio was presented for all treatment groups
Time frame: Months 6, 12, 18 and 24
Population: Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 6 (n=71,26,40,1) | 1.06 Ratio | 95% Confidence Interval 2.763 |
| Core: Deferasirox (ICL) | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 12(n=66, 29, 41, 1) | 1.17 Ratio | 95% Confidence Interval 3.654 |
| Core: Deferasirox (ICL) | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 18 (n=68, 26, 39, 1) | 1.24 Ratio | 95% Confidence Interval 5.112 |
| Core: Deferasirox (ICL) | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 24 (n=63, 25, 33, 1) | 1.38 Ratio | 95% Confidence Interval 5.277 |
| Core: Deferoxamine (DFO) | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 12(n=66, 29, 41, 1) | 1.06 Ratio | 95% Confidence Interval 2.68 |
| Core: Deferoxamine (DFO) | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 24 (n=63, 25, 33, 1) | 1.33 Ratio | 95% Confidence Interval 5.821 |
| Core: Deferoxamine (DFO) | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 6 (n=71,26,40,1) | 1.05 Ratio | 95% Confidence Interval 2.024 |
| Core: Deferoxamine (DFO) | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 18 (n=68, 26, 39, 1) | 1.18 Ratio | 95% Confidence Interval 3.748 |
| Extension; DFO to ICL | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 6 (n=71,26,40,1) | 1.03 Ratio | 95% Confidence Interval 2.778 |
| Extension; DFO to ICL | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 24 (n=63, 25, 33, 1) | 1.21 Ratio | 95% Confidence Interval 4.658 |
| Extension; DFO to ICL | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 18 (n=68, 26, 39, 1) | 1.13 Ratio | 95% Confidence Interval 4.376 |
| Extension; DFO to ICL | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 12(n=66, 29, 41, 1) | 1.07 Ratio | 95% Confidence Interval 3.411 |
| Extension: ICL to DFO | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 24 (n=63, 25, 33, 1) | 1.11 Ratio | 95% Confidence Interval 0 |
| Extension: ICL to DFO | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 6 (n=71,26,40,1) | 1.00 Ratio | 95% Confidence Interval 0 |
| Extension: ICL to DFO | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 12(n=66, 29, 41, 1) | 1.17 Ratio | 95% Confidence Interval 0 |
| Extension: ICL to DFO | Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment | Month 18 (n=68, 26, 39, 1) | 1.05 Ratio | 95% Confidence Interval 0 |
Secondary
Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24
Results of liver iron content (LIC) measurements by MRI was summarized by descriptive statistics. The absolute value and the absolute change from baseline in LIC at Months 6, 12, 18 and 24 were provided by treatment group.
Time frame: Months 6, 12, 18 and 24
Population: Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 6 (n=71,26,38,1) | -4.56 mg Fe/g dw | Standard Deviation 7.467 |
| Core: Deferasirox (ICL) | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 12 (n=69,29,40,1) | -10.22 mg Fe/g dw | Standard Deviation 10.674 |
| Core: Deferasirox (ICL) | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 18 (n=70,23,38,1) | -12.26 mg Fe/g dw | Standard Deviation 13.938 |
| Core: Deferasirox (ICL) | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 24 (n=60,24,33,1) | -15.74 mg Fe/g dw | Standard Deviation 15.205 |
| Core: Deferoxamine (DFO) | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 12 (n=69,29,40,1) | -19.44 mg Fe/g dw | Standard Deviation 11.446 |
| Core: Deferoxamine (DFO) | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 18 (n=70,23,38,1) | -26.09 mg Fe/g dw | Standard Deviation 13.443 |
| Core: Deferoxamine (DFO) | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 24 (n=60,24,33,1) | -26.02 mg Fe/g dw | Standard Deviation 14.867 |
| Core: Deferoxamine (DFO) | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 6 (n=71,26,38,1) | -12.66 mg Fe/g dw | Standard Deviation 7.821 |
| Extension; DFO to ICL | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 18 (n=70,23,38,1) | -10.87 mg Fe/g dw | Standard Deviation 11.116 |
| Extension; DFO to ICL | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 12 (n=69,29,40,1) | -7.98 mg Fe/g dw | Standard Deviation 9.31 |
| Extension; DFO to ICL | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 24 (n=60,24,33,1) | -10.96 mg Fe/g dw | Standard Deviation 11.07 |
| Extension; DFO to ICL | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 6 (n=71,26,38,1) | -6.30 mg Fe/g dw | Standard Deviation 7.375 |
| Extension: ICL to DFO | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 24 (n=60,24,33,1) | -3.20 mg Fe/g dw | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 12 (n=69,29,40,1) | -3.90 mg Fe/g dw | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 6 (n=71,26,38,1) | -3.80 mg Fe/g dw | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Month 18 (n=70,23,38,1) | -2.90 mg Fe/g dw | Standard Deviation 0 |
Secondary
Extension Study: Change in Serum Ferritin From Baseline by Month
Serum ferritin values was summarized by descriptive statistics. Absolute value and the absolute change from baseline in serum ferritin by month was provided by treatment group.
Time frame: Months 6, 12, 18 and 24
Population: Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 12 (n=70,29,40,1) | -988.46 ug/L | Standard Deviation 2883.416 |
| Core: Deferasirox (ICL) | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 6 (n=72,28,38,0) | -626.10 ug/L | Standard Deviation 1541.406 |
| Core: Deferasirox (ICL) | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 18 (n=66,24,39,1) | -1962.14 ug/L | Standard Deviation 2225.438 |
| Core: Deferasirox (ICL) | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 24 (n=59,24,30,0) | -2239.03 ug/L | Standard Deviation 2178.564 |
| Core: Deferoxamine (DFO) | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 12 (n=70,29,40,1) | -1877.00 ug/L | Standard Deviation 1877.745 |
| Core: Deferoxamine (DFO) | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 18 (n=66,24,39,1) | -2426.92 ug/L | Standard Deviation 2685.817 |
| Core: Deferoxamine (DFO) | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 6 (n=72,28,38,0) | -1307.14 ug/L | Standard Deviation 1520.877 |
| Core: Deferoxamine (DFO) | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 24 (n=59,24,30,0) | -2724.00 ug/L | Standard Deviation 2693.583 |
| Extension; DFO to ICL | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 6 (n=72,28,38,0) | -1054.87 ug/L | Standard Deviation 1967.651 |
| Extension; DFO to ICL | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 12 (n=70,29,40,1) | -1223.73 ug/L | Standard Deviation 1808.056 |
| Extension; DFO to ICL | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 24 (n=59,24,30,0) | -1513.23 ug/L | Standard Deviation 2278.144 |
| Extension; DFO to ICL | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 18 (n=66,24,39,1) | -1494.82 ug/L | Standard Deviation 1511.257 |
| Extension: ICL to DFO | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 24 (n=59,24,30,0) | NA ug/L | — |
| Extension: ICL to DFO | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 18 (n=66,24,39,1) | -1067.00 ug/L | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 12 (n=70,29,40,1) | -498.00 ug/L | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: Change in Serum Ferritin From Baseline by Month | Month 6 (n=72,28,38,0) | NA ug/L | — |
Secondary
Extension Study: The Cardiac Iron Concentration From T2* Values
Cardiac iron concentration (derived from T2\* values) at baseline, Months 6, 12, 18 and 24 were summarized by descriptive statistics. The absolute change from baseline at Months 6, 12, 18 and 24 were also summarized by treatment group. Lliver iron concentration is expressed in units (mg of iron / g of liver tissue dry weight (dw)
Time frame: Months 6, 12, 18 and 24
Population: Full Analysis Set (FAS): consisted of all patients enrolled in the extension. Patients were analyzed according to the treatment they were assigned to in the beginning of the extension phase
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core: Deferasirox (ICL) | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 18 (n=68,26,39,1) | -0.47 mg Fe/g dw | Standard Deviation 0.789 |
| Core: Deferasirox (ICL) | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 24 (n=63,25,33,1) | -0.70 mg Fe/g dw | Standard Deviation 0.834 |
| Core: Deferasirox (ICL) | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 6 (n=71,26,40,1) | -0.12 mg Fe/g dw | Standard Deviation 0.587 |
| Core: Deferasirox (ICL) | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 12 (n=66,29,41,1) | -0.38 mg Fe/g dw | Standard Deviation 0.674 |
| Core: Deferoxamine (DFO) | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 6 (n=71,26,40,1) | -0.12 mg Fe/g dw | Standard Deviation 0.539 |
| Core: Deferoxamine (DFO) | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 24 (n=63,25,33,1) | -0.69 mg Fe/g dw | Standard Deviation 0.989 |
| Core: Deferoxamine (DFO) | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 12 (n=66,29,41,1) | -0.12 mg Fe/g dw | Standard Deviation 0.695 |
| Core: Deferoxamine (DFO) | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 18 (n=68,26,39,1) | -0.45 mg Fe/g dw | Standard Deviation 0.797 |
| Extension; DFO to ICL | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 12 (n=66,29,41,1) | -0.14 mg Fe/g dw | Standard Deviation 0.49 |
| Extension; DFO to ICL | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 6 (n=71,26,40,1) | -0.08 mg Fe/g dw | Standard Deviation 0.465 |
| Extension; DFO to ICL | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 18 (n=68,26,39,1) | -0.20 mg Fe/g dw | Standard Deviation 0.607 |
| Extension; DFO to ICL | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 24 (n=63,25,33,1) | -0.34 mg Fe/g dw | Standard Deviation 0.863 |
| Extension: ICL to DFO | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 18 (n=68,26,39,1) | -0.24 mg Fe/g dw | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 12 (n=66,29,41,1) | -0.77 mg Fe/g dw | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 6 (n=71,26,40,1) | 0 mg Fe/g dw | Standard Deviation 0 |
| Extension: ICL to DFO | Extension Study: The Cardiac Iron Concentration From T2* Values | Month 24 (n=63,25,33,1) | -0.52 mg Fe/g dw | Standard Deviation 0 |